Pharmaceutically active ingredients (API) that are poorly soluble constitute a problem for many reasons, e.g. due to the slow dissolution profile of said API, when incorporated. For instance, when a pharmaceutical composition comprising an API being poorly soluble in water is taken orally, the drug must dissolve in aqueous gastrointestinal fluids, such as in patients' stomach or intestine, before it can exert a therapeutic effect. An API being “poorly soluble in water” is generally considered to be an API which has a solubility of less than or equal to 0.1 mg/ml in water as defined in the US or European Pharmacopoeia. A recurring problem with pharmaceutical compositions comprising poorly water soluble drugs is that the rate of dissolution of the drug limits its biological availability. Reduction of particle size (e.g. by micronization) is one of the most common methods used to increase the dissolution profiles of poorly soluble active ingredients.
In order to demonstrate such problems of representative critical situations and attempts to deal with such situations represented by the use of ezetimibe as an exemplified API being poorly soluble API in water, reference can for example be made to the following documents.
US 2007/0275052 discloses pharmaceutical compositions containing micronized particles of ezetimibe, and a process for preparing said pharmaceutical compositions. In this process, ezetimibe is blended with further ingredients, and the resulting blend was granulated with a binding solution to get granules. The granules were dried and finally compressed into tablets.
By further exemplified reference to another representative situation, EP 2 216 016 describes the dry preparation of a mixture containing the pharmaceutically active ingredient (API) ezetimibe, by sieving and mixing ezetimibe with hydrophilic excipients, by avoiding the use of water and organic solvents.
As a further exemplified reference, US 2004/0126423 A1 discloses a composition comprising a cholesterol absorption inhibitor and a HMG-CoA reductase inhibitor, one or more anti-oxidants, microcrystalline cellulose, hydroxypropyl methylcellulose (HPMC), magnesium stearate and lactose.
Another illustrative reference, WO 2007/003365, discloses pharmaceutical compositions, inter alia comprising ezetimibe as API. In preparing said compositions, it is described that the API is mixed with one or more controlled release agents and granulated by adding solvent in a shear mixer or by fluidized bed granulator. The resulting granulate is then dried and sized.
Still further illustrative WO 2008/101723 shows a pharmaceutical composition comprising ezetimibe and at least one hydrophilic polymer, wherein said ingredients are dissolved in organic solvent, followed by drying or and an optional step of further milling, sieving and filling into capsules or compressing into tablets, or wherein the solution is dispersed onto a suitable carrier.
However, despite the above described methods and preparations of formulations containing a poorly soluble API, there is a need for an improved process for the preparation of a pharmaceutical composition or dosage form, respectively, containing an API being poorly soluble in water, and for an improved pharmaceutical composition or dosage form, respectively, containing said API.